tbuckley/cabot-search huggingface dataset:
PB2113: TREATMENT REFRACTORINESS AND RESPONSE RATES IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: A RETROSPECTIVE ANALYSIS OF REAL-WORLD DATA
Authors: Zahra Majd, Ning Lyu, Hua Chen, Susan Abughosh
Journal: HemaSphere (2023)

Background: Despite significant progress in the treatment of multiple myeloma (MM), relapse rates remain high, leading to shorter response periods, poor prognosis, and lower survival rates, even with subsequent treatments. Aims: Given the limited real-world evidence, this study aimed to assess the treatment refractoriness and response rates among patients with relapsed and/or refractory MM. Methods: This was a retrospective study conducted among relapsed and/or refractory MM patients using a commercial registry. Patients were included in the study if they a) were 18-79 years of age at the time of diagnosis; b) received ≥ 5 lines of therapy; c) were exposed to at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD), and one CD38-targeting monoclonal antibody (CD38 MoAB); and d) had the last MM related visit before October 2022. Patients were excluded if they had concurrent primary malignancies or recorded death within 28 days of the last line initiation. Patients’ response status was defined by the International Myeloma Working Group (IMWG) Response Criteria (2016). Patients were categorized as “responders” if their response status lasted for at least 28 days. Refractoriness was defined by IMWG Response Criteria as progression while on treatment or within 60 days of treatment discontinuation. The class of refractoriness was additionally determined for each patient. “Penta-class” was defined as refractoriness to 1 CD38 MoAB + 2 PIs + 2 IMiDs, “triple-class” as refractoriness to an IMiD, a PI, and a CD38 MoAB, and “dual-class” as refractoriness to an IMiD and a PI. “Not triple” refractory was defined as refractoriness to 1 CD38 MoAB, and not both of a PI and an IMiD. Results: A total of 283 patients were included in the study with an age range of 27-78 years (median: 65). Patients received a median of 6 lines of therapy ranging from 5 to 21. The overall response rate among the patients was 35.7% (101 out of 283), with a median response duration of 6.3 months (range: 0.9-53.4). The majority of patients were classified as penta-refractory (33.6%), followed by dual-refractory (32.9%), triple-refractory (25.4%), and not triple-refractory classes (13.4%). The response rates were 49.1% in patients with dual-class, 44.7% in not triple-refractory, 33.7% in penta-class, and 22.2% in triple-class refractory. Summary/Conclusion: This real-world study indicates that a significant portion of patients continue to experience treatment refractoriness and have a low response rate even after multiple lines of therapy. These findings highlight the need for continued efforts to improve treatment outcomes and address the challenges of MM relapse and refractoriness. Keywords: relapsed/refractory, Multiple myeloma, Real world data
P1338: VASCULARIZED BONE MARROW-ON-CHIP TO STUDY VASCULAR ABERRATION IN HEMATOPOIETIC DISEASES
Authors: Thomas Bessy, Jessica Albuquerque, Jorgina Reginold, Lucas Sagnet, Giovanni Diana, Manuel Thery, Diana Passaro
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: The bone marrow (BM) is the main physiological site for adult hematopoiesis. BM niche is a complex tissue composed of different cell populations interconnected by a network of matrix proteins and vessels. Endothelial cells (ECs) lining the vessels actively participates in normal hematopoiesis and are dramatically remodeled in diseases affecting the bone (Stucker et al., 2020). We have observed a thorough remodeling of the vascular tree in the BM upon acute myeloid leukemia (AML) development by using mouse models of the disease and patient-derived xenografts, pointing towards the existence of an active crosstalk between the two compartments contributing to disease pathogenesis (Gomes AL, 2021; Passaro et al., 2017; Passaro, 2021). Aims: Being able to model the cross-talk between leukemia and the vascular BM niche in a humanized system is a key path toward the development of novel clinical strategies. Moreover, studying the vascular microenvironment in a flexible in vitro system that can be easily manipulated can progress our understanding of the fundamental mechanisms underlying its implication in disease (Bessy et al., 2021). Methods: We propose the generation of an all-in-one vascularized BM-on-chip (vBM-on-chip) with fully controlled cell deposition. We performed two-photon laser ablation to pattern a vascular tree in ECM hydrogel embedded in a PDMS chip in close proximity with bone-like structures. This chip connected with a microfluidics system can recapitulate the native BM vascular flow, with human ECs lining capillary-size vessels and associated with pericytes. Results: Our system is able to recapitulate the BM heterogeneity in terms of size, morphology and functional parameters (e.g., blood flow, permeability). Mathematical modelling allows the prediction of areas of flow perturbation favouring cell adhesion. Functionally, these vessels can sustain normal hematopoietic stem cell adhesion and maintenance in a quiescent or active state over time, as well as inducing multiple fate differentiation. This system is currently used as a target discovery platform to study AML patient-derived cell interaction with the vascular niche, monitor leukemia-driven vascular aberration over time and interfere with candidate targets to hamper AML-niche pathologic cross-talk. Summary/Conclusion: Our approach allows the generation of a fully humanized BM vascular niche unit in a microscopy friendly environment to follow in real time the local vascular environment for normal and malignant hematopoiesis with multimodal microscopy and molecular approaches, in order to develop targeted therapy that can normalize the vessels in BM diseases and promote better therapeutic success in patients.Keywords: Acute myeloid leukemia, Endothelial cell, Bone marrow microenvironment, Angiogenesis
P1289: DECIPHERING THE CLONAL ARCHITECTURE IN SECONDARY ACUTE MYELOID LEUKEMIA AND DONOR CELL-DERIVED MYELODYSPLASTIC SYNDROME BY SINGLE-CELL MULTI-OMICS ANALYSIS
Authors: Ken-Hong Lim, Lo-Ho Chen, Meng-Ta Sung, Ya-Wen Chiang, Jie-Yang Jhuang, Yu-Chen Chang, Caleb Gon-Shen Chen
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell diseases. Disease transformation into secondary myelofibrosis and acute myeloid leukemia (AML) negatively impact the outcome of MPNs and are frequently related to the clonal evolution of the disease subclones. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for patients with secondary AML (sAML). Donor-derived myelodysplastic syndrome (MDS) is a rare complication of HSCT and the incidence is estimated to be between 0.5% and 3%. Donor MDS can occur due to the transfer of malignant stem cells or pre-malignant clones from the donor to the recipient during HSCT. Aims: This study aimed to decipher the clonal architecture in a patient with JAK2 V617F-mutated essential thrombocythemia transformed to sAML and then developed donor MDS by single-cell multi-omics analysis over multiple treatment time points. Methods: Bulk next-generation sequencing (NGS) and customized Tapestri single-cell multi-omics DNA-protein panels were used to sequence peripheral blood and bone marrow samples at the time of sAML transformation, after complete hematologic remission, after sibling-matched allogeneic HSCT, and after the occurrence of donor MDS. A total of 10,049 cells from 4 samples of the patient were analyzed. Results: The results of bulk NGS revealed that the JAK2 V617F-mutated patient acquired IDH1 R132G and PHF6 I314T mutations at the time of sAML transformation, and all 3 mutations became undetectable after sibling-matched allogeneic HSCT. The results of single-cell multi-omics DNA-protein analysis revealed that the sAML subclone harbored all the 3 mutations (JAK2 V617F/IDH1 R132G and PHF6 I314T) and EZH2 loss. The sAML subclone has a significantly higher expression of CD71 (Figure 1). After sibling-matched allogeneic HSCT, a subclone from the donor cells was found to harbor EZH2 loss but the patient remained in complete remission. After being diagnosed with donor MDS due to progressive thrombocytopenia and bone marrow dysplasia, the patient remained 100% donor-type short tandem repeats. Single-cell multi-omics analysis showed that the donor MDS subclone harbored a TP53 mutation and EZH2 loss, and a JAK2 V617F-mutated subclone was also detected in donor cells. Interestingly, the donor MDS subclone also has a higher CD71 expression. Summary/Conclusion: The clonal architectures of sAML and donor MDS were clearly illustrated by single-cell multi-omics analysis in our study.Keywords: Clonal expansion, MDS, Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant
PB2695: ANALYSIS OF THE CURRENT SITUATION AND FACTORS INFLUENCING PSYCHOLOGICAL DISTRESS OF HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS IN THE LAMINAR FLOW WARD
Authors: Jing Wen, Jie Tang, Fangfang Wu, Aihua Sun
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: The incidence rate and mortality of blood tumor diseases are high, and the incidence rate of blood diseases is increasing year by year. Hematopoietic stem cell transplantation (HSCT) is a therapeutic method to transplant autologous or other hematopoietic stem cells into the body to restore normal hematopoietic and immune functions. It is one of the important means to treat various hematological diseases at present. Psychological distress is an unpleasant emotional experience caused by multiple factors. It is the most common psychological problem of HCST patients. It is listed as the sixth vital sign by the International Association of Psychological Oncology. Psychological distress can reduce the quality of life of patients and affect their health. We pay attention to the psychological status of patients while treating the disease Aims: To understand the status of psychological distress of patients with hematopoietic stem cell transplantation in laminar flow ward and analyze the possible influencing factors. Methods: 168 patients undergoing hematopoietic stem cell transplantation in our department from May to December 2022 were selected as the study subjects. The psychological distress temperature scale (including the psychological distress thermometer (DT) and the problem list (PL)) of the National Comprehensive Cancer Network (NCCN) and the general data questionnaire were used to conduct a cross-sectional survey of the patients, and the related factors of their psychological distress were analyzed by multivariate logistic regression. Results: A total of 168 valid questionnaires were collected. The investigated patients with hematopoietic stem cell transplantation had different levels of psychological distress. The patients’ gender, family income, medical insurance and commercial insurance reimbursement ratio, sleep disorders, physical symptoms after transplantation, time of transplantation in the warehouse, and no family company were related to the degree of psychological distress of patients with hematopoietic stem cell transplantation in the laminar flow ward (P<0.05). Summary/Conclusion: The incidence of psychological distress in patients with hematopoietic stem cell transplantation is high. In clinical nursing work, we should not only pay attention to the care of patients with physical diseases, but also pay more attention to the psychological status of patients, carefully evaluate the psychological status of patients and actively intervene in patients with psychological distress in time to reduce the degree of psychological distress of patients, so as to improve the compliance of patients with disease treatment. Keywords: Hematopoietic cell transplantation
PB2488: KIMURA’S DISEASE: A NEEDLE IN A HAYSTACK
Authors: Hind Hanani, Hajar Khibri, Wafa Ammouri, Mouna Maamar, Hicham Harmouche, Zoubida Tazi Mezalek, Mohamed Adnaoui
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Kimura’s disease is a rare but benign chronic inflammatory disease of unknown etiology and histological diagnosis. It usually affects young Asian men in their 2nd to 4th decade of life and typically manifests as painless subcutaneous nodules of the head and neck with satellite lymphadenopathy, eosinophilia and elevated serum total IgE. Endemic entity in the East but sporadic elsewhere with 300 cases described to date, we report the case of a patient in whom this diagnosis was retained after biopsy. Aims: To report a rare and benign cause of lymphadenopathy that could be confused with an hematologic malignancy; tuberculosis or other infectious lymphadenopathy. Methods: Description of a clinical case diagnosed and treated in an Internal Medicine department. Results: We present the case of a 17-year-old Libyan patient with a history of allergic rhinitis. He reports the appearance four years ago of a left jugal subcutaneous nodule which recurred 6 months after a first resection. One year later, a new nodule appeared in the right parotid region and multiple submental formations increasing in size treated by iterative antibiotic therapy with minimal reduction in size. On admission, a 6 cm subcutaneous nodule in the left cheek, a 4 cm one in the right parotid region and three centimetric submental adenopathies were observed, with no other local or general signs. These formations evoked on a cervico-facial CT a Hodgkin’s lymphoma. The histological study showed a parenchyma with a preserved architecture made up of lymphoid follicles with clear germinative centers, an enlarged interfollicular zone populated by numerous eosinophilic polymorphonuclear cells with microabscesses, hyperplasia of the post-capillary venules and interstitial fibrosis, this aspect evoking a Kimura’s disease.The complementary assessment found eosinophilia at 2069 elements/mm³ and a level of total serum IgE at 67.44 IU/mL. A CT scan confirmed the absence of distant localization and a bone marrow biopsy did not find any Reed-Sternberg cells. In view of the anamnesis ruling out any other cause and the histological aspect, Kimura’s disease was retained and prednisone (1 mg/kg/day) was initiated with a significant reduction in size without any recurrence. Summary/Conclusion: Kimura’s disease can be a source of medical wandering given its rarity. It should be considered in the presence of any recurrent cervico-facial nodule with eosinophilia and/or elevation of serum total IgE and underlines the importance of histology, which any clinician should resort to in case of doubt. The treatment remains poorly codified but involves corticosteroid therapy, surgery coupled with possible low-dose radiotherapy and involves the patient’s preferences.Keywords: Lymphoproliferative disorder
PB2587: BLOODSTREAM INFECTIONS AMONG PATIENTS WITH HEMATOLOGICAL MALIGNANCY IN ARMENIA
Authors: Diana Soghomonyan, Marieta Melksetyan, Gevorg Tamamyan, Karen Meliksetyan, Samvel Danelyan
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: During intensive treatment of hematological malignancies, such us chemotherapy or hematopoietic stem cell transplantation, the risk of blood stream infections (BSIs) is increased. BSIs are laboratory confirmed isolation of at least one Gram positive or Gram negative bacteria or other pathogen from blood samples. Aims: It was investigated the incidence of BSIs amongst patients with hematological malignancies and neutropenia and examined the changing spectrum of microorganism Methods: BSI data between January 2021 and December 2022 was reviewed..Peripheral blood samples (5-10 ml) were collected and inoculated in aerobic and anaerobic blood culture bottles. Results: During this period from 340 febrile cases 92 patients (27%) is blood culture positive. Among them 64.17% Gram positive (CoNS 32,79%, Enterococcus spp.16.3%,Staphylococcus aureus 8,6% viridans group Streptococci 5.4%) 31.49% Gram negative bacteria (Escherichia coli 11.95%, Enterobacter cloacae 6.52%, Pseudomonas aeruginosa 4.34%, other Gram negative bacteria such as Klebsiella spp. Proteus mirabilis, Acinetobacter spp. are 8.6%) and 4,34 % fungi. The amount of Gram negative cases during 2021 is 28.57%, while in 2022 is 32 %.. The amount of CoNS during 2021 is 28.5 while in 2022 is 40%. Summary/Conclusion: The Incidence of positive cases is 0.27.The most common isolates are CoNS, E.coli and Enterococcus spp.. The amount of Gram negative bacteria are increased in 10.8 % while CoNS is increased in 28.75%.These results could help clinicians to understand the epidemiology of BSIs and infection risk factors during chemotherapy courses. Keywords: Infection
PB2493: PERIPHERAL NEUROPATHY A HIDDEN CAUSE FOR PAIN IN GAUCHER DISEASE.A CASE REPORT AND REVIEW OF LITERATURE
Authors: Azza Abdel Gwad Tantawy, Khaled Anwar, Amira Adly, Nihal Hussien
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Pain is one of the disabling symptom in Gaucher disease, many studies investigated its etiology especially in Gaucher disease type 1.Peripheral neuropathy is a well established cause of pain in Fabry disease and sometime sin Pompe disease.Here we present a case of Gaucher disease type 1 with years of chronic pain proved to be due to peripheral neuropathy Aims: To study the relationship between Gaucher disease type 1 and peripheral neuropathy as a cause of pain Methods: Retrospective collection of data of diagnosis of young female patient diagnosed with Gaucher disease type 1 and analysis of the chronic pain the patient is suffering.Hematology, liver and kidney functions, serum vitamin B12, serum folic acid and nerve conduction velocity was done Results: A 29 years old female married patient of first cousin consanguineous parents, neither smoker nor alcoholic diagnosed as GD1 at the age of 22 years. Initial laboratory investigations were complete blood picture (CBC)showing (TLC:4.2*103/ul, Neut:2.09*103/ul, Lymph:1.8*103/ul, Hb:12.6 gm/dl, MCV:82fl, MCH:24.5 pg, plt:45*103/ul).Immunological markers were negative,bone marrow examination revealed infiltration by Gaucher cells.Plasma chitotriosidase was 2390 umol/L/h,beta glucocerberosidase was 0.7 umol/gmpr/h and her genetic analysis for GD revealed homozygous mutation for N409S(N370S).Her pelviabdominal ultrasound showed a liver volume of 1550cc and a spleen volume of 560cc.After 4 years of treatment she started to complain from chronic pain in her extremities especially in her lower limbs sometimes tingling and numbness in nature.By examination her weight is 62kg(50th centile), her height is 155cm(50th centile) with BMI 27kg/m2 with normalization of her abdominal examination.Her neurological examination is normal. Investigations done included CBC showing (TLC:5.1*103/ul, Neut:2.5*103/ul, Lymph:2.1*103/ul, Hb:13.7 gm/dl, MCV:82.7fl, MCH:27 pg, plt:45*136/ul), serum calcium of 9.3 mg/dl, serum magnesium of 1.8 mg/dl, serum phosphorous of 3.7 mg/dl, alkaline phosphatase of 73 u/l, fasting blood glucose of 90 mg/dl, glycated hemoglobin of 4.5 %, serum vitamin b12 of 300pg/ml, serum folic acid level of 5 ng/ml, glucosylsphingosine (lyso GL1) was 68.8 ng/ml.. Nerve conduction velocity of both peroneal and tibial nerves of both lower limbs showed reduced amplitude denoting axonal neuropathy together with delayed peak latency of both sural nerves. Summary/Conclusion: Polyneuropathy should be considered an important differential diagnosis in assessment of pain in GD especially type 1 as it is considered recently to be part of the natural history of GD 1.Pathophysiology and risk factors for developing peripheral neuropathy in GD 1 still needs more studies on large scale of patients. Keywords: Gaucher disease
PB2642: EVALUATION OF INNOVATIVE LABORATORY TESTS TO PREDICT A THROMBOTIC PHENOTYPE IN A FAMILY WITH DYSFIBRINOGENEMIA AND A NOVEL FGG MUTATION.
Authors: Amaury Monard, Fs.C.J.I. Heubel-Moenen, Elisabetta Castoldi, Ilaria De Simone, P.E.J. van der Meijden, Kanin Wichapong, W.P.T.M. van Doorn, Stefano Spada, D.L.S. Hellenbrand, A.D.M. Stork, Hugo Ten Cate, E.A.M. Beckers, Y.M.C. Henskens
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Hypodysfibrinogenemia is a rare hereditary fibrinogen disorder characterized by quantitative and qualitative fibrinogen defects. These fibrinogen defects can cause thrombotic and hemorrhagic phenotypes. Unfortunately, predicting the phenotype in a specific patient is often not possible with routine coagulation tests. Aims: To characterize the phenotype and the genetic profile of a family with hypodysfibrinogenemia and to investigate the ability of innovative tests to predict bleeding and/or thrombotic phenotypes in asymptomatic family members. Methods: The proband, a 60-year-old woman with both bleeding and thrombotic complications who is currently on DOAC treatment, and two daughters were referred to our Hemophilia Treatment Center (HTC) for phenotypical and genotypical analysis of a congenital fibrinogen disorder (CFD). Extensive laboratory testing was done, as well as DNA-sequence analysis and molecular modelling. Thrombin generation and microfluidic testing were also performed to investigate their ability in phenotype prediction. Results: Fibrinogen activity and antigen levels led to the diagnosis of dysfibrinogenemia in the proband and hypodysfibrinogenemia in both daughters. In all three cases, the same heterozygous missense mutation in the FGG gene was uncovered. This likely pathogenic mutation leads to the p.(Tyr375Cys) amino acid change. Molecular modeling predicted possible conformational changes or covalent dimerization of the fibrinogen molecule. Thrombin generation was elevated in one daughter. Microfluidic testing showed enhanced fibrin formation in both daughters, regardless of the coagulation trigger (figure 1). Summary/Conclusion: We described a family with hypodysfibrinogenemia in whom a novel heterozygous missense mutation in the FGG gene was found, possibly leading to conformational changes or covalent dimerization of the fibrinogen molecule. Furthermore we showed that microfluidic testing and thrombin generation can indicate a thrombotic phenotype in these patients, not detected with routine coagulation tests. Informed consent and approval from the medical-ethical committee from Maastricht (METC azM/UM) were obtained.Fig 1. Fluorescence microscopic images showing fibrin deposition, imaged at t=10 minutes. AF-647 fibrinogen was added to whole blood for detecting fibrin. Blood samples were recalcified with CaCl2/MgCl2 and perfused over collagen III or collagen I ± tissue factor (TF), at a shear rate of 1000s-1. Data obtained from daughters 1 and 2 were compared to 6 healthy donors. Scale bar = 40 µm. Keywords: Thrombosis, Gene mutation, Fibrinogen, Bleeding disorder